An American study entitled ‘Detection of early pancreatic ductal adenocarcinoma with thrombospondin-2 and CA19-9 blood markers’ was recently published in Science Translational Medicine.

The study, using complex cell programming techniques, was able to identify a molecule that would appear to have increased in patients with pancreatic cancer at an early stage.

If subsequent studies confirm what has been discovered so far, what avenues could be explored for the treatment of a tumor that is still the fourth most common cause of cancer death in Western countries?

We spoke about this topic with Professor Alessandro Zerbi, Head of Pancreatic Surgery at Humanitas, and with Dr. Paola Allavena, Head of the Laboratory of Cell Immunology at Humanitas.


The importance of markers in pancreatic cancer

“The effort in searching for markers for pancreatic cancer is long standing. We have often been confronted with the possibility of having identified a more effective one than the one already available, but the initial enthusiasm has diminished in the face of reality data. Even in the case of this study, therefore, a certain amount of caution is required, even though the data is important and valid,” emphasizes Professor Zerbi.

“The need for markers arises from a real need: the diagnosis of pancreatic cancer is late, with important repercussions in terms of treatment effectiveness. Having a blood test that could detect the disease early would significantly change the history of this type of cancer.


Results of the study

“Thanks to complex laboratory methods, the researchers were able to isolate some proteins and detected one in particular, thrombospondin 2, which was statistically increased in patients with pancreatic cancer, even at an early stage. A molecule that seems to be better than CA 19-9 (the marker currently available) because it also expresses itself in the early stages of the disease.

The combined use of the two markers could lead to the detection of pancreatic cancer, given that data showed that 98% of cancers produce either thrombospondin 2 or CA 19-9,” explains Professor Zerbi.


Possible areas of use

“If the results were approved and the product was commercially produced, we could imagine two areas of use: on one hand, in early detection, and on the other hand, in active surveillance programs.

In this regard, there is a project created by the Italian Association of Pancreas Studies, of which Professor Zerbi is president, which involves patients considered at risk for this tumor because they present an increased genetic risk due to family history. In fact, the presence of close relatives with pancreatic cancer exposes them to a greater risk of developing a disease.

“These subjects are followed in some Centers that have joined the programme, such as Humanitas, and are invited to undergo a series of examinations every year. If a blood test capable of detecting the disease at an early stage were developed, it would be much easier, even for these patients considered at risk”.


Research work in Humanitas

As Dr. Paola Allavena tells us, Humanitas is also involved in the identification of significant markers for pancreatic cancer.

“It is important to make early diagnosis of this tumor, only 10-15% of patients are operable, a very small number. Earlier diagnosis is therefore the objective to which a great deal of effort is also devoted in the field of research.

Our team is doing a long job, which started a few years ago. We know from the basic scientific literature that ductal carcinoma of the pancreas (the most dangerous form of pancreatic cancer) also has a pattern of disease progression. Ductal cells transform and proliferate; the first responsible for this mutation is the oncogene K-Ras, we know other molecules of genes involved, but K-Ras is the first to express itself”.


The proteomic investigation

“We therefore used some healthy pancreatic cells that could be grown in vitro and inserted the oncogene K-Ras, thus activating an initial carcinogenesis. We then thought of trying to identify which proteins were outside the cell, because it was possible that – if present in an extracellular environment – they could then find themselves in the blood and be measurable. Thanks to a sophisticated proteomic investigation, in collaboration with the Mario Negri Institute for Pharmacological Research, we have identified several dozen proteins. We then applied some selection parameters and chose some, until we arrived at a list of six. Out of these, we have validated four and identified two at the end: they are two matrix proteins that are normally not present in the plasma of healthy subjects. We have found that these two proteins are higher in the plasma of patients with pancreatic cancer.


The continuation of research work

“We will now focus on comparing protein levels with certain clinical parameters, such as the aggressiveness of the tumor and the time when the diagnosis was made, to see if we can get more information. In the future, it would be interesting to check whether patients who are developing pancreatic cancer (without this being evident yet) already have these plasma proteins.

The collaboration between the research world and the clinical field is therefore fundamental, we need each other in an attempt to find new ways for the benefit of patients,” concludes Dr. Allavena.